Erectile dysfunction (ED) is defined as the persistent inability to
achieve and/or maintain an erection sufficient for satisfactory sexual
performance. The combined prevalence of minimal, moderate and complete
ED was reported as high as 52% from the Massachusetts Male Aging
Study.[sup.1] At age 40, there is an about a 40% prevalence rate,
increasing to almost 70% in men at age 70.[sup.1] In Canada, a similar
overall prevalence of ED was reported (49.4%).[sup.2] In addition, ED
been shown to have a negative impact on a patient's quality of
life, sexual relationships and overall well-being.[sup.3] The etiology
of ED fits in one of 3 categories: organic, psychogenic or, most
commonly, a combination of both.

Phophodiesterase-5 (PDE) inhibitors revolutionized ED treatment and
is the first-line treatment. These agents have been shown to be
effective with good safety profiles in a comorbid population of men with
ED, including patients with vascular disease, coronary artery disease
(CAD), hypertension and diabetes.[sup.4]-[sup.6] Treatment options for
patients not responding to oral drugs (or contraindicated) include
intracavernous injections, intraurethral alprostadil,
vacuum-constriction devices and penile prosthesis.[sup.7]

ED, endothelial dysfunction and metabolic syndrome (MetS)

Vasculogenic ED and generalized vascular disease might have a
hypothetical link through a common pathophysiologic mechanism
"endothelial dysfunction," an inability of the smooth muscle
cells lining the arterioles to relax; this prevents vasodilatation.
Diabetic patients with ED exhibited abnormal blood pressure and
platelet-aggregation responses (markers of endothelial function) than
diabetic men without ED; this resulted in impaired arteriolar dilatation
and ED.[sup.8]

Metabolic syndrome is a complex of symptoms that includes obesity,
insulin resistance, hypertension and dyslipidemia. Most (if not all)
patients with metabolic syndrome report varying degrees of ED.[sup.9]
Therefore, endothelial dysfunction with reduced nitric oxide activity is
the link between metabolic syndrome and ED.[sup.10]

ED and silent (subclinical) coronary artery disease

An association between ED and CAD has been suggested based on
similar risk factors, in addition to the presence of endothelial
dysfunction as a trigger for the pathogenesis of atherosclerosis. A high
prevalence (up to 75%) of ED was reported in patients with established
CAD and, interestingly, the severity of ED, but not ED prevalence, was
significantly correlated with the number of coronary vessels
involved.[sup.11] However, the prevalence of silent CAD in the setting
of ED is under reported. Subclinical coronary artery atherosclerosis can
be detected non-invasively with the use of multi-slice computed
tomography (MSCT). Coronary artery calcification was more frequent in
individuals with ED than in age-matched controls with similar coronary
risk score.[sup.12] Furthermore, Vlachopoulos and colleagues reported
angiographically documented silent CAD in 19% of patients with
vasculogenic ED.[sup.13] Conversely, the extent and prevalence of
coronary artery calcification (atherosclerosis) in ED patients could not
be predicted by the presence of traditional risk factors for
cardiovascular disease.[sup.12]

ED and future cardiac events

Erectile dysfunction has been suggested to be an early sign of
generalized vascular disease; ED patients may be at risk of later
developing CAD.[sup.14] Additionally, ED is dependent on the presence
and extent of asymptomatic atherosclerosis, including that of the
coronary arteries, and precedes the development of clinically evident
CAD by a significant amount of time.[sup.12]-[sup.14] It was shown that
in patients with established CAD, ED was diagnosed in most CAD patients
by an average of 2 to 3 years, however, up to one third of patients with
CAD did not complain of ED.[sup.15] This is of great clinical importance
as timely intervention of cardiac risk factor in patients with ED who
are at risk of developing CAD could prevent future cardiac events. So
far, it is not clear whether why cavernous arteries are more sensitive
to systematic atherosclerosis (ischemia), than coronary arteries, in the
setting of generalized vascular inflammation and endothelial
dysfunction. One possible explanation is the "artery size
hypothesis" where cavernosal artery has a smaller diameter than the
larger vessels in the heart.[sup.16] Nevertheless, acute coronary
syndrome is more related to sudden plaque rupture rather than the
insidious course of progressive penile ischemia related to cavernous
artery disease.

Sexual dysfunction and cardiac risk

Patients with ED should be assessed initially during the history
taking to assess for the extent and type of cardiovascular status
present according to Princeton II Consensus Conference risk
stratification (Table 1). The low-risk category includes asymptomatic
patients with <3 cardiovascular risk factors, controlled
hypertension, mild-stable angina pectoris, post-revascularization with
no significant residual ischemia, myocardial infarction >6
weeks previously, mild valvular disease, left ventricular dysfunction
(New York heart association class I), pericarditis, mitral valve
prolapse and atrial fibrillation with ventricular response.[sup.17]
Patients with ED without these criteria fit into either intermediate- or
high-risk categories. Patients categorized as low-risk require no
special cardiac testing or evaluation prior to the initiation of
treatment for ED and resumption of sexual activity, and they can be
managed within primary care.[sup.17] Sexual activity should be deferred
until stabilization of cardiac condition in high risk category (Table
1). Patients in the intermediate-risk category require further cardiac
evaluation so that they can be definitively classified as low- or
high-risk (Fig. 1).

Rationale against routine cardiac assessment

We are not in favour of routine cardiac assessment for all ED
patients, especially, healthy individuals with low cardiac risk.
However, it is our practice to initiate cardiac risk stratification and
complete cardiac assessment for patients with intermediate- to high-risk
factors.[sup.17] Another important consideration is that not all ED
patients have arteriogenic causes (atherosclerosis); in contrast, a
small, but significant, proportion of patients have ED secondary to
veno-occlusive dysfunction, psychogenic ED, hypogonadism and neurogenic
causes. However, when a patient presents with ED, it is an excellent
occasion to modify some risk factors for CAD, such as smoking, to
prevent further vascular deterioration. Nevertheless, it is intuitive to
recommend cardiac assessment for patients with severe ED and
comorbidities, as stated before, especially when cavernous artery
disease present (low peak systolic velocity on penile duplex
ultrasound).[sup.11]

Initial assessment of cardiac status would include exercise
treadmill testing, which maybe a good predictor of cardiac ischemia
during sexual intercourse,[sup.18] before proceeding with more invasive
tests like angiography. Furthermore, there is emerging interest in a
number of plasma pro-inflammatory biomarkers (e.g., high-sensitive
C-reactive protein) which are simple blood tests; these biomarkers are
promising in the diagnosis of silent CAD in ED patients.[sup.19]

Modification of lifestyle factors in men with ED (i.e., weight
reduction and increase in physical activity) is the first step in
preventing future cardiovascular events.[sup.20] Conversely, it is not
clear whether modification of lifestyle factors has a great impact on
ED, however, improvement in lifestyle factors is associated with huge
positive impact on overall health.

Conclusion

Cardiac workup in patients seeking medical advice for ED should be
considered for intermediate- to high-risk patients. Lifestyle changes
and medical therapy for ED are safe and have additional benefits in
treating ED treatment and reducing the risk of future cardiac
events.